Healthy Volunteers With IleostomyPhase 1/2NCT02473640

A Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Adults With an Ileostomy

A Phase 1/2 study testing SYN-004, Esomeprazole and Ceftriaxone in people with Healthy Volunteers With Ileostomy, run by Theriva Biologics, Inc. at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A Phase 1b/2a, Multi-Center, Open-Label, 2-Period, Fixed-Sequence Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Healthy Adult Subjects with a Functioning Ileostomy Read more about this study

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers With Ileostomy
What is being tested?: SYN-004, Esomeprazole and Ceftriaxone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 2 sitesCanada
Study dates: Jun 2015to Apr 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

The subject has a functioning ileostomy that has been in place for ≥ 3 months.
The subject is male or female between the ages of 18 and 80 years, inclusive.
Other than a functioning ileostomy, the subject is free from clinically significant illnesses or disease.

Who cannot join

Subjects who have active hepatic, small intestine, or biliary tract disease.
Subjects who have active ulcerative colitis, Crohn's disease, other inflammatory bowel disease.
Subjects with known malignancy requiring treatment < 6 months prior to study screening.
Subjects who have, in the opinion of the investigator, significant concurrent medical illness.
Subjects who are currently taking concomitant medications which may interfere with study evaluation.
Subjects who have received an investigational drug within 30 days or within a time period consistent with a washout period of 5 half-lives, whichever is longer, of the first dose of ceftriaxone.

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Subjects with a known history of allergy to any cephalosporin, penicillin or any β-lactam antibiotic.
Subjects who have known active malabsorption syndromes(s) that, in the judgment of the investigator, could compromise the objectives of the study.
Subjects who have used any oral, intramuscular, or IV anti-microbial medication during the last 3 week

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

Synthetic Biologics Investigative Site
Edmonton, Alberta
Synthetic Biologics Investigative Site
Montreal

Other trials in Canada

About this study

Official title: A Phase 1b/2a, Multi-Center, Open-Label, 2-Period, Fixed-Sequence Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Healthy Adult Subjects With a Functioning Ileostomy

Read the detailed description

This is a Phase 1b/2a, randomized, multi-center, open-label study. Twenty otherwise healthy subjects with functioning ileostomies who are between the ages of 18 and 80 years, inclusive, will be enrolled. The entire duration of the study may be up to 63 days (from Screening to the end-of-study [EOS] visit).

Conditions: Healthy Volunteers With Ileostomy
Being tested: SYN-004, Esomeprazole, Ceftriaxone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SYN-004Drug
EsomeprazoleDrug
CeftriaxoneDrug

Study groups in NCT02473640
Study group	Role	What they receive
150 mg SYN-004	Experimental	There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of steady-state esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home. Receives: Drug: SYN-004; Drug: Esomeprazole; Drug: Ceftriaxone

What is being measured

The primary outcome is the main question the study is designed to answer.

Ceftriaxone Concentration in Intestinal Chyme Period 1
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Measured: 0-8.5 hours
Ribaxamase Concentration in Intestinal Chyme Period 1
Concentrations of ribaximase (SYN-004) in intestinal chyme
Measured: 0-8.5 hours
Ceftriaxone Concentration in Intestinal Chyme Period 2
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Measured: 0-8.5 hours
Ribaxamase Concentration in Intestinal Chyme Period 2
Concentrations of ribaximase (SYN-004) in intestinal chyme
Measured: 0-8.5 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2015Apr 2016

First posted16 Jun 2015 (estimated)
Study startJun 2015
Primary completionApr 2016
Study completionApr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy Volunteers With IleostomyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02473640
Sponsor's protocol ID: SB-1-004-004
Status last verified: Oct 2018
First submitted: 12 Jun 2015
Last updated: 27 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kokai-Kun JF, Roberts T, Coughlin O, Sicard E, Rufiange M, Fedorak R, Carter C, Adams MH, Longstreth J, Whalen H, Sliman J. The Oral beta-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e02197-16. doi: 10.1128/AAC.02197-16. Print 2017 Mar.
PubMed 28052855

Study at a glance

From the registry record, last updated by the sponsor on 27 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b/2a, Multi-Center, Open-Label, 2-Period, Fixed-Sequence Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Healthy Adult Subjects With a Functioning Ileostomy
ClinicalTrials.gov ID: NCT02473640
Acronym / sponsor ID: SB-1-004-004
Conditions: Healthy Volunteers With Ileostomy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Theriva Biologics, Inc.Industry (pharma, biotech, devices)
Study start: Jun 2015
Primary completion: Apr 2016 (actual)
Study completion: Apr 2016 (actual)
First posted: 16 Jun 2015 (estimated)
Results: Posted 19 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
150 mg SYN-004	Experimental	Drug: SYN-004, Drug: Esomeprazole, Drug: CeftriaxoneThere will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of steady-state esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

The subject has a functioning ileostomy that has been in place for ≥ 3 months.
The subject is male or female between the ages of 18 and 80 years, inclusive.
Other than a functioning ileostomy, the subject is free from clinically significant illnesses or disease.

Key exclusion criteria (9 listed)

Subjects who have active hepatic, small intestine, or biliary tract disease.
Subjects who have active ulcerative colitis, Crohn's disease, other inflammatory bowel disease.
Subjects with known malignancy requiring treatment < 6 months prior to study screening.
Subjects who have, in the opinion of the investigator, significant concurrent medical illness.
Subjects who are currently taking concomitant medications which may interfere with study evaluation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SYN-004	Drug	150 mg SYN-004
Esomeprazole	Drug	150 mg SYN-004
Ceftriaxone	Drug	150 mg SYN-004

Primary outcome

Ceftriaxone Concentration in Intestinal Chyme Period 1
Time frame: 0-8.5 hours
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Ribaxamase Concentration in Intestinal Chyme Period 1
Time frame: 0-8.5 hours
Concentrations of ribaximase (SYN-004) in intestinal chyme
Ceftriaxone Concentration in Intestinal Chyme Period 2
Time frame: 0-8.5 hours
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Ribaxamase Concentration in Intestinal Chyme Period 2
Time frame: 0-8.5 hours
Concentrations of ribaximase (SYN-004) in intestinal chyme

Results and safety

Results posted to the registry on 19 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
150 mg SYN-004	15	14

Primary outcome: Ceftriaxone Concentration in Intestinal Chyme Period 1

Time frame: 0-8.5 hours. Mean (Standard Error). Unit: ug/mL

Measure	150 mg SYN-004 n = 14
Hour 0	0.00 (0.00)
Hour 0.5	0.00 (0.00)
Hour 1.5	5.60 (4.39)
Hour 2.5	150.90 (68.43)
Hour 3.5	231.40 (144.06)
Hour 4.5	173.00 (98.58)
Hour 5.5	29.00 (25.40)
Hour 6.5	1.40 (0.82)

Population analysed: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.

Primary outcome: Ribaxamase Concentration in Intestinal Chyme Period 1

Time frame: 0-8.5 hours. Mean (Standard Error). Unit: ng/mL

Measure	150 mg SYN-004 n = 14
Hour 0	0.00 (0.00)
Hour 0.5	2 (2.1)
Hour 1.5	11 (9.1)
Hour 2.5	131 (116.8)
Hour 3.5	6727 (3983.1)
Hour 4.5	56795 (25155.4)
Hour 5.5	73090 (29292.8)
Hour 6.5	103171 (52510.2)

Primary outcome: Ceftriaxone Concentration in Intestinal Chyme Period 2

Time frame: 0-8.5 hours. Mean (Standard Error). Unit: ug/mL

Measure	150 mg SYN-004 n = 14
Hour 0	0.00 (0.00)
Hour 0.5	0.00 (0.00)
Hour 1.5	9.80 (8.43)
Hour 2.5	31.70 (22.57)
Hour 3.5	42.80 (30.44)
Hour 4.5	80.50 (56.28)
Hour 5.5	0.80 (0.63)
Hour 6.5	0.10 (0.10)

Population analysed: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.

Primary outcome: Ribaxamase Concentration in Intestinal Chyme Period 2

Time frame: 0-8.5 hours. Mean (Standard Error). Unit: ng/mL

Measure	150 mg SYN-004 n = 14
Hour 0	0.00 (0.00)
Hour 0.5	436 (435.6)
Hour 1.5	281 (206.6)
Hour 2.5	97745 (74180.)
Hour 3.5	66936 (46358.5)
Hour 4.5	63696 (26962.2)
Hour 5.5	42316 (15114.4)
Hour 6.5	38874 (21552.0)

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Period 1	0 of 15 (0%)	3 of 15 (20%)	0 of 15
Run-in Period	0 of 14 (0%)	3 of 14 (21.4%)	0 of 14
Treatment Period 2	0 of 14 (0%)	2 of 14 (14.3%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28052855Kokai-Kun JF, Roberts T, Coughlin O, Sicard E, Rufiange M, Fedorak R, Carter C, Adams MH, Longstreth J, Whalen H, Sliman J. The Oral beta-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e02197-16. doi: 10.1128/AAC.02197-16. Print 2017 Mar.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing SYN-004, Esomeprazole and Ceftriaxone in people with Healthy Volunteers With Ileostomy, run by Theriva Biologics, Inc. at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ceftriaxone Concentration in Intestinal Chyme Period 1 (time frame: 0-8.5 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02473640, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2018.